# Dietary modulation of gut microbiome and host gene expression across human evolution and the emergence of modern human disease

> **NIH NIH R01** · J. CRAIG VENTER INSTITUTE, INC. · 2020 · $313,952

## Abstract

Evidence suggests that lifestyle changes, concordant with the adoption of agriculture and industrialization, have
impacted the emergence of the so-called diseases of modern civilization in humans (e.g. metabolic disorders,
cardiovascular disease etc.). The incidence of these diseases in contemporary, industrialized populations is
believed to be associated with a lack of adaptation of our genomes to the rapid dietary and lifestyle changes that
occurred across human evolution. However the usefulness and resolution of this evolutionary model of disease
are limited. Moreover, although the dietary and genetic markers of human evolution have been studied, we still
lack understanding on how the microbiome, our second genome, has interacted with nutritional and host-
genomic axes to confer increased disease risk in modern humans. Preliminary data by our group show that
dietary shifts significantly modulate the gut microbiome and metabolome of wild primates, our closest
evolutionary relatives. Additionally, we have identified gut microbiome markers only found in populations
representing Paleolithic lifestyles (hunter-gatherers) and distinguishing them from traditional agriculturalists and
industrialized populations. Thus, given 1) the potential role of diet in human evolution, 2) the critical impact of
the gut microbiome on the nutritional and immune landscape of mammals, and 3) the existence of gut
microbiome patterns exclusive of hunter-gatherers, we hypothesize that the emergence of metabolic disease in
modern humans was significantly mediated by interactions between diet, the gut microbiome and the human
genome across evolution. These issues are still unexplored. Thus, in Aim 1 of this proposal we will use a multi-
OMIC approach (gut metabolomics, metagenomics and transcriptomics of the host colonic tissue) to identify
metabolic and genetic markers that emerged and/or were lost when humans transitioned from hunter-gatherer
to agricultural and industrialized lifestyles, and in humans affected by metabolic disease phenotypes. In Aim 2,
we will use integrated meta-OMICs and network theory approaches to predict metabolic disease phenotypes,
from hunter-gatherers to, populations in transition to agriculture to modern populations at risk. This system-level
study will broaden our understanding of the extrinsic (environmental/nutritional) and intrinsic factors
(genetic/metabolic) impacting the evolution of modern human disease. Additionally, the evolutionary approach
proposed will shed light on potentially novel diet and microbe-based translational strategies to mitigate the
incidence of metabolic disease in contemporary human populations.

## Key facts

- **NIH application ID:** 9892997
- **Project number:** 5R01DK112381-03
- **Recipient organization:** J. CRAIG VENTER INSTITUTE, INC.
- **Principal Investigator:** Harinder Singh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $313,952
- **Award type:** 5
- **Project period:** 2017-07-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892997

## Citation

> US National Institutes of Health, RePORTER application 9892997, Dietary modulation of gut microbiome and host gene expression across human evolution and the emergence of modern human disease (5R01DK112381-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9892997. Licensed CC0.

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